摘要：

 Antisense oligonucleotides (AON) are being developed for a wide array of therapeutic applications. Significant improvements in their serum stability, target affinity, and safety profile have been achieved with the development of chemically modified oligonucleotides. Here, we compared 2′-deoxy-2′-fluoro-β-D-arabinonucleic acid (FANA)-containing AONs with phosphorothioate oligodeoxynucleotides (PS-DNA), 2′-O-methyl-RNA/DNA chimeras and short interfering RNAs (siRNA) with respect to their target knockdown efficacy, duration of action and resistance to nuclease degradation. Results show that two different configurations of FANA/DNA chimeras (altimers and gapmers) were found to have potent antisense activity. Specific target inhibition was observed with both FANA configurations with an estimated EC₅₀ value comparable to that of an siRNA but 20-to 100-fold lower than the other commonly used AONs. Moreover, the FANA/DNA chimeras showed increase

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